title: Parathyroid hormone therapy mollifies radiation-induced biomechanical degradation in murine distraction osteogenesis.
abstract: OBJECTIVE
  Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration.
  
  
  METHODS
  Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 µg/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ≤ 0.05.
  
  
  RESULTS
  Parathyroid hormone-treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles.
  
  
  CONCLUSIONS
  The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration-approved drug on formulary, significantly improve outcomes in a model of postoncologic craniofacial reconstruction.
authors.affiliation: Ann Arbor, Mich. From the University of Michigan Medical School, C. S. Mott Children's Hospital, and the University of Michigan Medical Center.
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Gallagher
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Tchanque-Fossuo
authors.forename: Deniz
authors.initials: D
authors.lastname: Sarhaddi
authors.forename: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000528:radiation effects; D015519:Bone Density / Q000187:drug effects / Q000528:radiation effects; D001861:Bone Regeneration / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D060733:Electromagnetic Radiation; D005500:Follow-Up Studies; D007279:Injections, Subcutaneous; D008297:Male; D008334:Mandible / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D019857:Osteogenesis, Distraction / Q000379:methods*; D010025:Osteoradionecrosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D016896:Treatment Outcome; D016474:Weight-Bearing
chemical_list: D010281:Parathyroid Hormone